Tasquinimod Clinical Trials

What Is Tasquinimod?

Tasquinimod is an investigational drug classified as a quinoline-3-carboxamide analog. It has been studied for its potential role in treating various cancers. In clinical trials, tasquinimod has shown promise by demonstrating improvements in progression-free survival and overall survival in men with castration-resistant prostate cancer (CRPC).

Currently, tasquinimod is being evaluated in clinical trials for a range of conditions. These include different forms of prostate cancer, such as prostate cancer, advanced or metastatic hepatocellular cancer, advanced or metastatic ovarian cancer, bone-only metastatic castration-resistant prostate cancer, hormone-resistant prostate cancer, metastatic castrate resistant prostate cancer, and metastatic prostate carcinoma. It is also under investigation for metastatic renal cell cancer, multiple myeloma, and myelofibrosis.

A total of 11 trials have been conducted or are ongoing for tasquinimod, involving 2,052 participants. The first trial began in 2007, and the latest started in 2024. Two trials are currently recruiting participants, while five have been completed.

Uses and Conditions Under Study

Tasquinimod is an investigational drug primarily studied for its potential in treating various cancers. Clinical trials have explored its effects across several different types of malignancies.

A significant focus of research has been on prostate cancer. This includes studies in general prostate cancer (4 trials), as well as more specific forms such as bone-only metastatic castration-resistant prostate cancer (1 trial), hormone-resistant prostate cancer (1 trial), metastatic castrate resistant prostate cancer (1 trial), and metastatic prostate carcinoma (1 trial). Tasquinimod, a quinoline-3-carboxamide analog, has shown the ability to improve progression-free survival and overall survival in men with castration-resistant prostate cancer in some studies, suggesting its potential to slow disease progression in these advanced stages.

Beyond prostate cancer, tasquinimod is also being investigated for other advanced or metastatic cancers. These include advanced or metastatic hepatocellular cancer (1 trial), advanced or metastatic ovarian cancer (1 trial), and metastatic renal cell cancer (1 trial). For these conditions, tasquinimod is being evaluated for its potential to impact tumor growth and spread. Additionally, it is under study for its effects in multiple myeloma (1 trial) and myelofibrosis (1 trial), two distinct blood cancers where new treatment options are continuously sought.

Overall, tasquinimod has been studied in 11 clinical trials involving 2,052 participants across these diverse cancer types. These trials aim to understand its safety and effectiveness in managing these challenging diseases.

Dosing

Tasquinimod is administered orally as capsules. In clinical trials, it has been studied at various dose levels, typically taken once daily.

Initial dosing often began at 0.25 mg per day. Depending on tolerability and study protocol, this dose was frequently titrated upwards. For example, some protocols involved increasing the dose to 0.5 mg per day after a period, and then potentially to a maximum of 1 mg per day. If patients experienced tolerability issues at higher doses, their dose could be reduced.

Specific dosing regimens explored in trials include:

• Tasquinimod as a single agent, with dose escalation and expansion phases.
• Tasquinimod in combination with other treatments, such as Radium-223 for patients with bone metastases from castration-resistant prostate cancer, or in combination with IRd (Ixazomib, Lenalidomide, Dexamethasone) for other conditions.
• Different dose levels for specific cohorts, such as those with hepatocellular carcinoma, ovarian carcinoma, or renal cell carcinoma.

The precise dose and schedule of tasquinimod can vary based on the specific condition being studied and whether it is used as a single agent or in combination with other therapies.

Side Effects

In clinical trials involving patients taking Tasquinimod, the most common side effects included:

• Fatigue: 29.6% of patients taking Tasquinimod experienced fatigue, compared to 21.4% on placebo.
• Decreased appetite: 25.5% of patients taking Tasquinimod experienced decreased appetite, compared to 8.3% on placebo.
• Back pain: 17.6% of patients taking Tasquinimod experienced back pain, compared to 13.3% on placebo.
• Constipation: 17.6% of patients taking Tasquinimod experienced constipation, compared to 6.7% on placebo.
• Asthenia (lack of energy): 13.3% of patients taking Tasquinimod experienced asthenia, compared to 9.2% on placebo.
• Oedema peripheral (swelling in limbs): 10.9% of patients taking Tasquinimod experienced peripheral oedema, compared to 6.7% on placebo.
• Anemia (low red blood cell count): 9.1% of patients taking Tasquinimod experienced anemia, compared to 3.3% on placebo.

Clinical Trial Results

Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

In a proof-of-concept study (NCT01732549) for patients with mCRPC who were not progressing after docetaxel-based chemotherapy, Tasquinimod showed mixed results:

• Patients taking Tasquinimod had a median time of 42.3 weeks before needing further anticancer treatment for prostate cancer, compared to 29.0 weeks for those on placebo.
• The median time to radiological progression-free survival (PFS) was 31.7 weeks for patients on Tasquinimod, compared to 22.7 weeks for those on placebo. This means Tasquinimod extended the time before cancer progression was seen on imaging.
• However, patients on Tasquinimod experienced a greater decrease in quality of life, with a median EuroQol-5 Dimension (EQ-5D) VAS score change of -9.0, compared to -3.5 for placebo (a more negative score indicates greater deterioration).
• Similarly, the time to deterioration in the Functional Assessment of Cancer Therapy - Prostate (FACT-P) was shorter for patients on Tasquinimod (median 8.1 weeks) compared to placebo (median 15.7 weeks), indicating a faster decline in functional well-being.

Another study in Asian chemo-naïve patients with mCRPC (NCT02057666) found that:

• The median time to radiological progression-free survival (PFS) was 11.00 months for patients on Tasquinimod, compared to 7.53 months for those on placebo.

Multiple Cancer Types (Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers)

A study (NCT01743469) investigated Tasquinimod in various advanced cancers:

Hepatocellular Carcinoma Cohort:

• Clinical benefit was observed in 32.1% of participants.
• The median progression-free survival (PFS) was 15.71 weeks.
• The median overall survival (OS) was 29.29 weeks.

Gastric Carcinoma Cohort:

• No clinical benefit was observed in participants (0.0%).
• The median PFS was 6.00 weeks.
• The median OS was 21.57 weeks.

Ovarian Carcinoma Cohort:

• Clinical benefit was observed in 20.0% of participants.
• The median PFS was 8.00 weeks.
• Median overall survival data was not available for this cohort.

Renal Cell Carcinoma Cohort:

• Clinical benefit was observed in 15.8% of participants.
• The median PFS was 14.86 weeks.
• The median OS was 32.71 weeks.

Currently Recruiting Trials

Tasquinimod is currently being investigated in clinical trials, offering potential new treatment options for patients with specific blood cancers. These studies aim to understand how Tasquinimod works, either alone or in combination with other therapies, and to evaluate its safety and effectiveness.

One ongoing study, NCT06605586, is a Phase 1/Phase 2 trial focusing on patients with myelofibrosis (MF). This study is designed for individuals whose myelofibrosis has not responded to, or who cannot tolerate, previous treatment with a Janus kinase (JAK) inhibitor. The trial seeks to improve therapy for these patients and plans to enroll approximately 20 participants. It is sponsored by Stichting Hemato-Oncologie voor Volwassenen Nederland.

Another important study, NCT06327100, is an open-label Phase 1/Phase 2 trial. This study is exploring Tasquinimod in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocytosis myelofibrosis (Post-ET MF). Researchers are investigating whether Tasquinimod, either by itself or when combined with ruxolitinib, can help manage these conditions. This trial aims to enroll 33 participants and is sponsored by M.D. Anderson Cancer Center.

Where to Participate

For patients interested in participating in the currently enrolling Tasquinimod trials, the primary location for the M.D. Anderson Cancer Center study (NCT06327100) is in Houston, Texas. This site is currently the only listed location for this particular study.

Eligibility criteria for this trial specify that participants must be between 18 and 18 years of age. The study is open to individuals of all genders, but it does not include healthy volunteers or children. Patients considering participation should discuss these criteria with their healthcare provider to determine if they might be a suitable candidate.

Development Timeline

The journey of Tasquinimod in clinical development began on November 19, 2007, with its first recorded trial. Since then, the drug has been investigated across a total of 11 clinical trials, involving over 2,000 participants. The development has progressed through various phases, including three Phase 1 trials, four Phase 2 trials, two Phase 1/Phase 2 trials, and two Phase 3 trials, with the latest trial starting on September 20, 2024.

Several organizations have played a crucial role in advancing Tasquinimod, including Ipsen, Active Biotech AB, M.D. Anderson Cancer Center, and Stichting Hemato-Oncologie voor Volwassenen Nederland, among others. Initially, Tasquinimod was explored for conditions such as IBS-C and hyperphosphatemia. Over time, its potential applications expanded significantly to include a wide range of cancers, particularly in the areas of:

• Advanced or Metastatic Ovarian Cancer
• Bone-only Metastatic Castration-Resistant Prostate Cancer (CRPC)
• Hormone-Resistant Prostate Cancer
• Metastatic Castrate Resistant Prostate Cancer
• Metastatic Prostate Carcinoma
• Metastatic Renal Cell Cancer
• Multiple Myeloma
• Myelofibrosis
• Primary Myelofibrosis and related myelofibrosis types
• Advanced or Metastatic Gastric Carcinoma

This broad exploration highlights the ongoing commitment to understanding Tasquinimod's potential across diverse and challenging medical conditions.